[SOFFCO-MM guidelines for the resumption of bariatric and metabolic surgery during and after the Covid-19 pandemic]. / Recommandations de la SOFFCO-MM en vue de la reprise de l'activité de chirurgie bariatrique et métabolique pendant et après la pandémie Covid-19.

Bariatric/metabolic surgery was paused during the Covid-19 pandemic. The impact of social confinement and the interruption of this surgery on the population with obesity has been underestimated, with weight gain and worsened comorbidities. Some candidates for this surgery are exposed to a high risk of mortality linked to the pandemic. Obesity and diabetes are two major risk factors for severe forms of Covid-19. The only currently effective treatment for obesity is metabolic surgery, which confers prompt, lasting benefits. It is thus necessary to resume such surgery. To ensure that this resumption is both gradual and well-founded, we have devised a priority ranking plan. The flow charts we propose will help centres to identify priority patients according to a benefit/risk assessment. Diabetes holds a central place in the decision tree. Resumption patterns will vary from one centre to another according to human, physical and medical resources, and will need adjustment as the epidemic unfolds. Specific informed consent will be required. Screening of patients with obesity should be considered, based on available knowledge. If Covid-19 is suspected, surgery must be postponed. Emphasis must be placed on infection control measures to protect patients and healthcare professionals. Confinement is strongly advocated for patients for the first month post-operatively. Patient follow-up should preferably be by teleconsultation.

SOFFCO-MM guidelines for the resumption of bariatric and metabolic surgery during and after the Covid-19 pandemic.

Bariatric/metabolic surgery was paused during the Covid-19 pandemic. The impact of social confinement and the interruption of this surgery on the population with obesity has been underestimated, with weight gain and worsened comorbidities. Some candidates for this surgery are exposed to a high risk of mortality linked to the pandemic. Obesity and diabetes are two major risk factors for severe forms of Covid-19. The only currently effective treatment for obesity is metabolic surgery, which confers prompt, lasting benefits. It is thus necessary to resume such surgery. To ensure that this resumption is both gradual and well-founded, we have devised a priority ranking plan. The flow charts we propose will help centres to identify priority patients according to a benefit/risk assessment. Diabetes holds a central place in the decision tree. Resumption patterns will vary from one centre to another according to human, physical and medical resources, and will need adjustment as the epidemic unfolds. Specific informed consent will be required. Screening of patients with obesity should be considered, based on available knowledge. If Covid-19 is suspected, surgery must be postponed. Emphasis must be placed on infection control measures to protect patients and healthcare professionals. Confinement is strongly advocated for patients for the first month post-operatively. Patient follow-up should preferably be by teleconsultation.

Apolipoprotein A-I proteolysis in aortic valve stenosis: role of cathepsin S.

Aortic valve stenosis (AVS) is the most common valvular heart disease in the Western world. Therapy based on apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins, results in AVS regression in experimental models. Nevertheless, apoA-I degradation by proteases might lead to suboptimal efficacy of such therapy. An activatable probe using a quenched fluorescently labeled full-length apoA-I protein was generated to assess apoA-I-degrading protease activity in plasma derived from 44 men and 20 women with severe AVS (age 65.0 ± 10.4 years) as well as from a rabbit model of AVS. In human and rabbit AVS plasma, apoA-I-degrading protease activity was significantly higher than in controls (humans: 0.038 ± 0.009 vs 0.022 ± 0.005 RFU/s, p < 0.0001; rabbits: 0.033 ± 0.016 vs 0.017 ± 0.005 RFU/s, p = 0.041). Through the use of protease inhibitors, we identified metalloproteinases (MMP) as exerting the most potent proteolytic effect on apoA-I in AVS rabbits (67%, p < 0.05 vs control), while the cysteine protease cathepsin S accounted for 54.2% of apoA-I degradation in human plasma (p < 0.05 vs control) with the maximum effect seen in women (68.8%, p < 0.05 vs men). Accordingly, cathepsin S activity correlated significantly with mean transaortic pressure gradient in women (r = 0.5, p = 0.04) but not in men (r = - 0.09, p = 0.60), and was a significant independent predictor of disease severity in women (standardized beta coefficient 0.832, p < 0.001) when tested in a linear regression analysis. ApoA-I proteolysis is increased in AVS. Targeting circulating cathepsin S may lead to new therapies for human aortic valve disease.

Beneficial Effects of High-Density Lipoproteins on Acquired von Willebrand Syndrome in Aortic Valve Stenosis.

BACKGROUND: Infusions of apolipoprotein A-I (apoA-I), the major protein component of high-density lipoproteins (HDL), result in aortic valve stenosis (AVS) regression in experimental models. Severe AVS can be complicated by acquired von Willebrand syndrome, a haemorrhagic disorder associated with loss of high-molecular-weight von Willebrand factor (vWF) multimers (HMWM), the latter being a consequence of increased shear stress and enhanced vWF-cleaving protease (ADAMTS-13) activity. Although antithrombotic actions of HDL have been described, its effects on ADAMTS-13 and vWF in AVS are unknown. METHODS AND RESULTS: We assessed ADAMTS-13 activity in plasma derived from a rabbit model of AVS (n = 29) as well as in plasma collected from 64 patients with severe AVS (age 65.0 ± 10.4 years, 44 males) undergoing aortic valve replacement (AVR). In both human and rabbit AVS plasma, ADAMTS-13 activity was higher than that in controls (p < 0.05). Accordingly, AVS patients had less HMWM than controls (66.3 ± 27.2% vs. 97.2 ± 24.1%, p < 0.0001). Both ADAMTS-13 activity and HMWM correlated significantly with aortic transvalvular gradients, thereby showing opposing correlations (r = 0.3, p = 0.018 and r = -0.4, p = 0.003, respectively). Administration of an apoA-I mimetic peptide reduced ADAMTS-13 activity in AVS rabbits as compared with the placebo group (2.0 ± 0.5 RFU/sec vs. 3.8 ± 0.4 RFU/sec, p < 0.05). Similarly, a negative correlation was found between ADAMTS-13 activity and HDL cholesterol levels in patients with AVS (r = -0.3, p = 0.045). CONCLUSION: Our data indicate that HDL levels are associated with reduced ADAMTS-13 activity and increased HMWM. HDL-based therapies may reduce the haematologic abnormalities of the acquired von Willebrand syndrome in AVS.

A sphingosine-1-phosphate receptor 1 agonist inhibits tertiary lymphoid tissue reactivation and hypersensitivity in the lung.

Hypersensitivity pneumonitis is characterized by pulmonary accumulation of B-cell-rich tertiary lymphoid tissues (TLTs), which are alleged sites of amplification for antigen-specific responses. The sphingosine-1-phosphate receptor 1 (S1P1) regulates key mechanisms underlying lymphoid tissue biology and its chemical modulation causes lymphocyte retention in lymph nodes. Given the putative immunopathogenic impact of lymphocyte accumulation in TLTs, we investigated whether or not chemical modulation of S1P1 caused lymphocyte retention within TLTs in a model of hypersensitivity pneumonitis. Mice were exposed subchronically to Methanosphaera stadtmanae (MSS) in order to induce an hypersensitivity pneumonitis-like disease. MSS exposure induced B-cell-rich TLTs surrounded by S1P1-positive microvessels. Upon MSS rechallenge, the S1P1 agonist RP001 prevented the pulmonary increase of CXCL13, a chief regulator of B-cell recruitment in lymphoid tissues. This was associated with a complete inhibition of MSS rechallenge-induced TLT enlargement and with a 2.3-fold reduction of MSS-specific antibody titers in the lung. Interference with TLT reactivation was associated with a 77% reduction of neutrophil accumulation and with full inhibition of protein-rich leakage in the airways. Thus, an S1P1 agonist hinders TLT enlargement upon antigenic rechallenge and inhibits key pathognomonic features of experimental hypersensitivity pneumonitis.

Omega-3 polyunsaturated fatty acids provided during embryonic development improve the growth performance and welfare of Muscovy ducks (Cairina moschata).

The welfare of ducks can be affected by unwanted behaviors such as excessive reactivity and feather pecking. Providing long-chain n-3 polyunsaturated fatty acids (LC n-3 PUFA) during gestation and early life has been shown to improve the brain development and function of human and rodent offspring. The aim of this study was to test whether the pecking behavior of Muscovy ducks during rearing could be reduced by providing LC n-3 PUFA during embryonic and/or post-hatching development of ducklings. Enrichment of eggs, and consequently embryos, with LC n-3 PUFA was achieved by feeding female ducks (n-3F) a diet containing docosahexaenoic (DHA) and linolenic acids (microalgae and linseed oil). A control group of female ducks (CF) was fed a diet containing linoleic acid (soybean oil). Offspring from both groups were fed starter and grower diets enriched with DHA and linolenic acid or only linoleic acid, resulting in four treatment groups with 48 ducklings in each. Several behavioral tests were performed between 1 and 3 weeks of age to analyze the adaptation ability of ducklings. The growth performance, time budget, social interactions, feather growth, and pecking behavior of ducklings were recorded regularly during the rearing period. No significant interaction between maternal and duckling feeding was found. Ducklings from n-3F ducks had a higher body weight at day 0, 28, and 56, a lower feed conversion ratio during the growth period, and lower reactivity to stress than ducklings from CF ducks. Ducklings from n-3F ducks also exhibited a significantly reduced feather pecking frequency at 49 and 56 days of age and for the whole rearing period. Moreover, consumption of diets enriched with n-3 PUFA during the starter and grower post-hatching periods significantly improved the tibia mineralization of ducklings and the fatty acid composition of thigh muscles at 84 days of age by increasing the n-3 FA content.

Postural stability limits in manifest and premanifest Huntington's disease under different sensory conditions.

Increasing evidence indicates that Huntington's disease (HD) produces postural control impairments even before the clinical diagnosis. It has been suggested that postural disorders of HD patients are explained by deficits in the processing and integration of sensory information, but this hypothesis has been under-explored. In the present study, we evaluated the amplitude of the center of pressure (COP) displacement during maximum leaning in four directions (forward, backward, rightward and leftward) and under three sensory conditions (eyes open, eyes closed and eyes closed standing on foam). We assessed the stability limits in 20 individuals with a positive HD genetic test (12 premanifests; eight manifests HD) and 15 healthy controls. The COP displacements were analyzed during the first and second phases of maintenance of the maximum leaning position. Manifest HD patients showed significantly greater COP ranges than healthy controls in both learning phases and all sensory conditions, but the greatest deterioration of their performance was found in the foam condition. In contrast, premanifest HD patients displayed larger COP ranges than controls only during the second phase of maximum learning, especially in the foam condition. Furthermore, both HD groups had significantly smaller limits of stability than healthy subjects during the second phase of maximum learning. However, their ability to maintain the maximum leaning position was degraded during both learning phases. Together, these findings demonstrate that HD reduces the limits of stability even before the clinical disease onset. Furthermore, our results indicate that dynamic postural tasks with high demand for sensorimotor integration and especially the use of proprioception are highly sensitive to early HD disease processes. This dynamic postural task may become a useful biomarker of HD progression.

Ibuprofen dependence: a case report.

Ibuprofen is currently widely prescribed and has not been reported to produce dependence. We report the case of a 17-year old patient who presented many positive psychic symptoms related to a pharmacological dependence. During the treatment, she adjusted herself posology as she developed withdrawal symptoms. Pharmacological evidences (effect on COX-1 and COX-2, FAAH and PPARs) allow us to formulate hypotheses explaining this effect.

Use of inactivated bluetongue virus serotype 8 vaccine against virulent challenge in sheep and cattle.

The immunisation properties of an inactivated bluetongue virus serotype 8 (BTV-8) vaccine were evaluated in sheep and cattle. Five sheep were vaccinated with one dose of vaccine and five cattle were vaccinated with two doses 28 days apart. Six sheep and five cattle served as unvaccinated controls. All animals were subjected to a virulent BTV-8 challenge, and safety and antibody responses were monitored. All control animals developed disease and viraemia, while vaccinated animals were clinically protected and viraemia was completely prevented.

Protective duration of immunity of an inactivated bluetongue (BTV) serotype 2 vaccine against a virulent BTV serotype 2 challenge in sheep.

The protective properties of an inactivated bluetongue virus serotype 2 (BTV-2) vaccine were evaluated in sheep. Sheep (two groups of seven), vaccinated with either one or two doses of the vaccine, were monitored for antibody response over one year. All sheep developed high titres of neutralizing antibodies by 35 days after first vaccination and titres were maintained over one year. Control sheep (n=7) remained seronegative until challenge. One year after vaccination, all sheep were inoculated with a virulent BTV-2. All controls developed pyrexia, clinical signs and viraemia. In contrast, the sheep vaccinated with one or two doses of inactivated BTV-2 vaccine were protected from clinical disease and viraemia was completely prevented. These data show that a single dose of the BTV-2 vaccine given to sheep induces a strong immunity which confers protection for at least one year.

Modulation of airway inflammation and resistance in mice by a nicotinic receptor agonist.

Nicotinic agonists, including 1,1-dimethyl-4-phenylpiperazinium (DMPP), have anti-inflammatory properties and in some instances smooth muscle relaxing effects. Since inflammation and airway smooth muscle contraction are two major components of asthma, the present authors investigated the effects of DMPP on airway inflammation and airway resistance in a mouse model of asthma. Mice were sensitised and challenged with ovalbumin (OVA) and treated either intraperitoneally or intranasally with DMPP. The effect of DMPP was tested on airway inflammation, airway resistance and on the increase of intracellular calcium in bronchial smooth muscle cells. DMPP given either during sensitisation, OVA challenges or throughout the protocol prevented lung inflammation and decreased the serum level of OVA specific immunoglobulin E. DMPP administration reduced the number of total cells, lymphocytes and eosinophils in the bronchoalveolar lavage (BAL) fluid. Intranasal DMPP administration was as effective as dexamethasone (DEXA) in reducing total cell count and eosinophil counts in BAL fluid. DMPP, but not DEXA, reduced tissue inflammation. Intranasal DMPP, given 10 min before the test, reduced airway responsiveness to metacholine. DMPP also reduced the increase in intracellular calcium in response to bradykinin. In conclusion, these results show that 1,1-dimethyl-4-phenylpiperazinium reduces lung inflammation and prevents airway hyperresponsiveness in the mouse model of asthma.

[Necrotizing bacterial skin and software tissue infection with muscular involvement revealing of cancer of the colon]. / Dermohypodermite bactérienne nécrosante (DHBN) avec atteinte musculaire à Clostridium septicum révélatrice d'un cancer du côlon.

We report the case of a 38-year-old woman with a necrotizing bacterial skin and soft tissue infection with muscular involvement. The clinical picture was similar to a gaseous gangrene of the right lower limb with a septic shock and multiple organ failure, without predisposing factor such as trauma, and necessitating a hip amputation. The primary site of the disease was a perforated colic adenocarcinoma with peritoneal and retroperitoneal infection. The association of necrotizing skin and soft tissue infection with muscular involvement due to Clostridium septicum to a neoplasma is classical and in front of such an infection a neoplasma should be researched.

[Total pancreatectomy for mucinous pancreatic tumor]. / Pancréatectomie totale pour tumeur mucineuse du pancréas.

AIM OF THE STUDY: To report our experience of total pancreatectomy (TP) in ten patients with mucinous pancreatic tumors (MPT), to discuss pre and peroperative investigations in the management of MPT, and operative, functional and carcinologic results after TP. PATIENTS AND METHODS: This retrospective study from January 1985 to January 2001 included ten patients, 5 men and 5 women (mean aged: 64 years). Six patients underwent one step TP for intraductal papillary mucinous tumor of the pancreas (IPMT) in 5 cases, and multifocal mucinous cystadenoma in one case. Four patients underwent a second step TP for tumor recurrence (2 IPMT, and 2 cystadenocarcinomas) which occurred 12 to 121 months post operatively (mean: 49 months). RESULTS: Post TP diabetes was controlled by insulinotherapy (3 injections a day), except in one patient who needed insulin administration through a pump. One patient, with cystadenocarcinoma, died from cancer recurrence 18 months after TP and 140 months after the initial pancreaticoduodenectomy. One patient died from heart disease 34 months postoperatively. The 8 other patients were alive with a mean follow-up of 33 months (range 11-61 months). CONCLUSION: Curative surgery for mucinous tumors of the pancreas may require TP, which is indicated preoperatively according to imaging, or intraoperatively following surgical findings and frozen section of the pancreatic margin. Totalization of a previous partial pancreatectomy is mandatory in case of tumoral persistence or recurrence in the pancreatic remnant. Postoperative diabetes can be managed successfully by a specialized team.

[Proximal bile duct cholangiocarcinomas]. / Cholangiocarcinomes de la voie biliaire principale proximale.

AIM: The aim of this retrospective study was to report a series of 12 patients with hilar cholangiocarcinoma treated by curative resection. PATIENTS AND METHODS: Between 1980 and 1998, curative resection was performed in 12 patients out of 33 patients with a Klatskin's tumor. Preoperative biliary drainage was performed in 6 cases. Resection was limited to the extrahepatic bile duct in one case only. Resection was extended to the liver in 11 cases including segmentectomy I (n = 9), left hepatectomy (n = 7), right hepatectomy (n = 3) and segmentectomy IV (n = 1). Postoperative brachytherapy was performed in 3 patients combined with conventional radiotherapy. Conventional radiotherapy irradiation was performed in 2 patients and was associated with chemotherapy in 1 patient. RESULTS: There was no postoperative mortality. Postoperative follow-up was uneventful in 5 patients. Actuarial survival rate at 1, 2, 3, and 5 years was 81, 57, 28 and 28%, respectively. Prolonged survivals (88 and 114 months) were observed. CONCLUSION: Hilar cholangiocarcinomas have a poor prognosis. Curative resections are usually performed with major liver resections. RM cholangiography is now the most efficient examination for selection of surgical indications and choice of the best strategy. Long-term survival can be obtained with curative surgery. Adjuvant treatment has to be assessed by controlled trials.

[Value of preoperative drainage of the bile ducts in obstructive jaundice]. / Intérêt du drainage préopératoire des voies biliaires en cas d'ictère obstructif.

Hepato-biliary surgery for obstructive jaundice is associated with high morbidity and mortality rates. Experimental and clinical studies on obstructive jaundice revealed endotoxaemia, coagulation disorders and depressed immune function. Many studies have been carried out to identify the operative risk factors. The serum bilirubin level seemed to be a significant factor. Biliary decompression via a percutaneous or endoscopic retrograde approach was therefore proposed to improve the surgical outcome. The first retrospective studies have suggested a reduction of morbidity and mortality. Subsequent randomized studies have not confirm the benefit of preoperative biliary drainage because of procedure-related complications. The article reviews the literature on preoperative biliary drainage and proposes the indications, choice of method and optimal duration of biliary drainage.

Routine determination of morphine, morphine 3-beta-D-glucuronide and morphine 6-beta-D-glucuronide in human serum by liquid chromatography coupled to electrospray mass spectrometry.

A robust liquid chromatographic mass spectrometric method capable of quantifying morphine, morphine 3-beta-D-glucuronide and morphine 6-beta-D-glucuronide down to 1.0 ng/ml, 5.0 ng/ml and 2.0 ng/ml respectively in human serum is presented. The method was validated over linear ranges of 1.0 to 20.0 ng/ml for morphine, 5.0 to 500.0 ng/ml for morphine 3-beta-D-glucuronide and 2.0 to 100.0 ng/ml for morphine 6-beta-D-glucuronide using deuterated morphine as internal standard. In tandem mass spectrometry conditions, the product ions of morphine-3-glucuronide and morphine-6-glucuronide were the ion m/z corresponding to the morphine moiety. By contrast morphine which presented numerous product ions after collision did not allowed a tandem methodology. Compounds were extracted on 100 mg C18 columns and analysed on the PE Sciex API 300 system equipped with a C18 column and electrospray ionisation interface. The interrun precision of quality controls (1.0, 2.0, 10.0, 20.0 ng/ml for morphine, 5.0, 10.0, 250.0, 500.0 ng/ml for morphine 3-beta-D-glucuronide and 2.0, 4.0, 50.0, 100.0 ng/ml for morphine 6-beta-D-glucuronide) was < or =9.3% and accuracy was between 97.9 and 109.8% for each analyte. Sample stabilities in biological matrix were also investigated. This method has been applied to pharmacokinetic analysis of morphine, morphine 3-beta-D-glucuronide and morphine 6-beta-D-glucuronide in human serum.